Cell Cycle Control and Cell Division Flashcards
Extracellular signal that suppress programmed cell death (apoptosis)
Survival factors
Activation of the Cyclin-Cdk complex is prerequisite for ______, however the activity of each complex is finely regulated by additional mechanisms
downstream events
Each _____ is important for determining which specific targets are subsequently phosphorylated by the Cdk subunit.
cyclin partner
Cdk-Activating kinase
CAK
The cell-cycle control depends on _______ regulation
transcriptional
In the absence of cyclin, Cdk is in an ____ state.
inactive
E2F proteins are inhibited by an interaction between E2F and the _____
retinoblastoma protein (Rb) family
protein involved in cell cycle regulation.
Rb: retinoblastoma protein
Where are the 3 checkpoint controls of cell cycle?
Late G1 or Start Checkpoint; G2-M Checkpoint; Metaphase to anaphase transition
The concentrations of the _____ oscillate during the cell cycle
three major cyclin proteins
______ causes proteolysis that works to degrade gemenin
APC/C
APC/C activity changes during the cell cycle due to its interactions with _____ in anaphase and ____ from late mitosis through early G1.
Cdc20; Cdh1
____ is a CKI family member that binds to the active cyclin-Cdk complex.
p27
The ______ system is designed to block progression through each of the checkpoints if problems are sensed
cell cycle control system
T/F: Just as mutations that alter cyclin or Cdk function can lead to misregulation of the cell cycle, so too can mutations that disrupt any of these regulatory mechanisms create the possibility that a cancer of some type may occur.
True
the process by which sister chromatids of duplicated DNA are separated and divided into daughter nuclei. Know the various phases of the mitosis and what happens during each.
Mitosis
______ of proteins is a key step in the initiation of many proteins “marked” for degradation by the proteasome complex.
Ubiquitylation
Cdk inhibitor protein
CKI
Ubiquitin ligase like APC/C;Contains 3 subunits; Ubiquitylates Cdk inhibitor (CKI) proteins in late G1 such as p27.
SCF
_____ phosphorylates the Rb protein, rendering it inactive and reducing its binding to E2F. This frees E2F to activate expression of its target genes.
G1-Cdk
The _____ binds exclusively to deacteylated histone H4
dREAM complex
ubiquitin ligase involved in cell-cycle control; named after its three subunits.
SCF
_______ Triggers the events that occur in each phase of the cell cycle; Ensures the proper timing, order and fidelity of the events; Responds to intracellular and extracellular signals; Arrests the cycle whenever the cell fails to complete and essential cell-cycle process or encounters unfavorable intracellular or extracellular conditions
cell-cycle control system
During ____ 2 sets of daughter chromosomes arrive at the poles of the spindle and decondense; a new nuclear envelope reassembles around each set; division of the cytoplasm begins with contraction of the contractile ring
telophase
genes that turn on and turn off dependent upon cues from environment, hormones, etc., that need to be present in the cell.
Inducible gene expression
induces assembly of the mitotic spindle, chromosome condensation, promotes breakdown of the nuclear envelope, rearrangements of the actin cytoskeleton and the Golgi apparatus
M-Cdk
The 2nd checkpoint allows the cell cycle to continue if what happens?
If environment is favorable and all DNA is replicated
Degradation of the _____ cyclins leads to inactivation of the Cdks.
S- and M-
The ______ triggers the major events of the cell cycle
cell-cycle control system
During ___ chromosomes are aligned at the equator of the spindle, midway between the spindle poles
metaphase
One of the key functions of G1-Cdk is to activate the______ that are themselves gene regulatory factors
E2F proteins
Prenatal growth retardation dealing with the ESCO2 gene
Roberts syndrome
Extracellular signal that stimulate cell division mainly by stimulating G1/S-Cdk activity that inhibit intracellular negative controls that block progression through the cell-cycle.
mitogens
____ is activated in mid-mitosis and remains active in G1, which provides a period in which Cdk is inactive
APC/C
_____ starts abruptly with the breakdown of the nuclear envelope; chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movement
Prometaphase
If chromosome is unattached to spindle, what halts cell cycle?
APC/C
Generally occurs due to a lack of growth factors or nutrients; Occurs in cells when they reach maturity; i.e become terminally differentiated, such as nerve cells, heart muscle cells and bone osteocytes.
G0 phase
Cells can remain in G0 for _____ or longer before resuming proliferation
days to weeks
family of proteins that regulator Cdk activity
Cyclin
S-Cdk, M-Cdk, and G1/S-Cdk inhibit the progression of cell cycle in presence of _____
DNA damage
is involved in protecting the protein linkages that hold the sister chromatids together; degradation leads to activation of a protease that then separates the sisters and unleashes anaphase
Securin
The cell-cycle control system depends on ______ events
cyclical proteolytic
T/F: Cyclin gene expression is regulated and specific cyclins genes are induced (turned on) as the cell cycle transitions from one phase to the next
True
Gene which encodes an acetyltransferase important for the formation of the cohesion complex that binds to chromosomes and creates cohesion between sister chromatids; mutations lead to decreased rDNA transcription and decreased protein synthesis
ESCO2
The appearance and disappearance of the various _____ are critical for determining the transitions from one phase of the cell-cycle to the next.
cyclins
Binding of the specific cyclin to its cognate cyclin-dependent kinase leads to a movement of the T-loop away from the active site, leading to ______
partial activation
What are the 3 extracellular signals controlling cell division?
Mitogens, growth factors, and survival factors
Abrupt increases in ____ activity at the G2-M checkpoint drives entry into mitosis and the events of early mitosis
M-Cdk
Cells enter G0 from a cell-cycle checkpoint in the ____ phase
G1 phase
_____ interact with cell surface receptors to trigger multiple intracellular signaling pathways
Mitogens
When the G1/S-Cdks are activated in late G1, APC/C is _____
turned off
____ associated co-activators promote transcription
E2F
Loss of the ____ means that their targets can be dephosphorylated by various phosphatases that are present in anaphase, which completes M phase.
Cdks
____ associates with an F-box protein that is required for binding to specific protein targets
SCF
_____ checkpoint insures that all of the DNA has been properly replicated
The G2-M checkpoint
prereplication complex assembles at the origins of replication at what point?
Late mitosis-early G1:
T/F: Many of the genes (proteins) involved in cell-cycle regulation are critical determinants of cancer progression.
True
DNA replication occurs at specific sites called _____
origins of replication
The first checkpoint allow the cell cycle to continue if what happens?
If environment is favorable
cell-division-cycle genes; important in cell cycle checkpoint control
Cdc
____ represents a resting or quiescent state in cell cycle
G0
_____ is essentially inappropriate proliferation
Cancer
____ can then phosphorylate the T-loop at a threonine residue in the T-loop resulting in full activation of the cyclin-Cdk.
Cdk-activating kinase (CAK)
The complexes are also regulated by various ______, which provide information about the extracellular environment, DNA or cell damage and whether each step in the cell-cycle has been properly completed
inhibitory mechanisms
As the cell cycle proceeds a series of _______ insure that each phase is complete before the next one begins.
of transitions or checkpoints
2 additional proteins ___ and _____ assist in the addition of multiple ubiquitin molecules to the CKI and this targets the protein for degradation in the proteasome complex
E1 and E2
During ____ the sister chromatids synchronously separate to form 2 daughter chromosomes and each is pulled slowly toward the spindle pole it faces; kinetochore microtubules get shorter and the spindle poles also move apart; contribute to chromosome segregation
anaphase
____ is thought to promote cell cycle entry by increasing the expression of the genes encoding the G1 cyclins (D cyclins), which results in increased G1-Cdk (cyclin D-Cdk4) activity
Myc
In the inactive state the catalytic or active site of the cyclin-dependent kinase is blocked by the presence of a region called the ______
T-loop
protein complex bound to origin of replication sites in DNA
ORC: origin recognition complex:
(genes that are turned on very early or almost immediately after a mitogen binds to its receptor)
immediate early gene expression
The 3rd checkpoint allows the cell cycle to continue if what happens?
If all chromosomes are attached to the spindle
T/F: Cells can enter G0 permanently until the cell dies
True
The activity of cyclin-Cdk is further regulated by _____, which further phosphorylates Cdk and renders it inactive and by Cdc25 phosphatase that dephosphorylates and restores activity
Wee1 kinase
Extracellular signal that stimulate cell growth (increase in cell mass) by stimulating protein synthesis and inhibiting protein degradation
Growth factors
Where does the 2nd checkpoint of cell cycle occur?
G2/M
Cytoplasm is divided in 2 by a contractile ring of actin and myosin filaments which pinches the cell in 2 to create 2 daughters, each with 1 nucleus
cytokinesis
What are the phases of mitosis
Prophase, Prometaphase, Metaphase, Anaphase, and Telophase
The cell cycle checkpoint control system depends on cyclically activated _____
cyclin-dependent protein kinases (Cdks)
The concentrations of the ____ do not change (constitutive expression)
Cdk
How many checkpoints or the cell cycle are there?
3
regulatory transitions in the cell-cycle in which the cell cycle will be arrested unless specific prior biochemical events are fully completed
Cell cycle checkpoints
Cyclin-dependent kinase (Cdk) requires the binding of ____ and subsequent specific phosphorylation to become an active enzyme
cyclin
anaphase promoting complex or cyclosome
APC/C
Passage through the Start Checkpoint in late G1 launches ____ and __ phase of cell cycle
DNA replication and the S phase of the cell cycle.
The cell-cycle involves DNA replication and dividing the cell to create ______
two identical daughter cells
In addition, the _______ initiates the metaphase to anaphase transition.
Anaphase-Promoting Complex or Cyclosome (APC/C)
family of protein kinases involved in the control of the cell-cycle
Cyclin-dependent kinases (Cdks)
genes that are expressed at a constant level throughout the life of a cell.
Constitutive gene expression
The expression of the 3 major cyclin proteins is _____
induced
During _____, the replicated chromosomes each consisting of 2 closely associated sister chromatids condense
prophase
complex of proteins involved in cell cycle control arrest and senescence by binding to the E2F family of transcription factors.
dREAM
Where does the 3rd checkpoint of cell cycle occur?
In M phase between Metaphase and Anaphase
Each _____ can induce different effects at different times in the cell-cycle based upon the relative presence, absence or abundance of each specific target, which can change depending upon the phase of the cell cycle.
cyclin-Cdk
The first checkpoint of the cell cycle occurs at what point?
G1/S phase
Member of the ubiquitin ligase family of proteins; Catalyzes the ubiquitylation and degradation of securin and the S- and M-cyclins.
APC/C
____ binds to both the cyclin and the Cdk subunits. This distorts the active site of the Cdk and also inserts into the ATP-binding site, further inhibiting the enzyme activity
p27
The central component of the control system is the series of _____ that regulate transitions through the various phases
cyclin-Cdk complexes
____ and ___ lead to histone modifications that result in histone compaction and suppression of gene expression
E2F and pRB
